Positron emission tomography (PET) is a very sensitive non-invasive imaging technology for measuring biochemical processes at a whole body level. One of the major roadblocks which limits the widespread use of this powerful technology in both preclinical and clinical settings is the availability of PET probes. New approaches are needed to enable biologists and clinicians to synthesize a wide range of PET probes. Integrated microfluidic technology with intrinsic advantages of speed, chemical economy, flexibility, user- friendliness, safety, modularity and low cost is a prime technology platform for producing radiolabeled molecular probes. Over the past three years, our research groups have demonstrated that integrated microfluidic devices can be used for efficient production of PET probes. In this proposal, we will create an automated, user-friendly and cost efficient microfluidic platform to facilitate syntheses and labeling of [18F]- labeled PET probes, and several small molecule- and bimolecule-based [18F]-labeled PET probes with sizes ranging from 1 to 10 nm will be produced using these microfluidic platform. Initially, we will develop three separate microfluidic functional modules in parallel, including: (i) An off-chip module for concentration of [18F]fluoride, (ii) the core-a set of digitally controlled microfluidic circuits for reagent mixing, solvent exchange, deprotection and/or functional group transformations. (Here, polyperfluoropolyether (PFPE)-elastomer will be utilized to fabricate this core module to achieve improved chemical inertness and device robustness), and (iii) an in-line purification and characterization system. We will assemble the three functional modules into an integrated device, which will be hosted in a standalone, light- weight, self-shielded hot cell, equipped with a digitally controlled interface. Based on a breadboard concept, we will build two new types of integrated devices with relatively more complicated device configurations to meet the synthetic protocols of two major categories of PET probes, i.e., small molecules and radiolabeled biomolecules. We will simplify and generalize the device design and the module connections to allow "plug-in" device reconfiguration. In parallel, a user-friendly operation interface will be developed for broader implementation of the proposed technology. We will then test the feasibility to quickly build new devices for producing novel PET probes. The resulting [18F]-labeled compounds will be evaluated through our collaborative efforts in our research Institute. This proposal brings together the expertise of eight research groups covering the fields of radiochemistry, microfluidics, polymer materials, device prototyping, molecular imaging and antibody engineering. We envision the success of proposed of research will provide a powerful, universal technology to allow a convenient supply of a wide range of [18F]-labeled PET probes, accelerate the discovery and development processes o new PET probes, and facilitate a broader implementation of PET imaging. PUBLIC HEALTH RELEVANCE: Our idea is to create a modular, automated and user-friendly microfluidic platform capable of synthesizing and labeling known and novel [18F]-labeled positron emission tomography (PET) imaging probes on demand. The long term objective of this proposal is to make [18F]-labeled PET probes easily accessible so that researchers and clinicians can perform a wide range of PET studies targeting specific molecular lesions in cancer.